Transforming growth factor-β1 attenuates inflammation and lung injury with regulating immune function in ventilator-induced lung injury mice

Ren, Jing; He, Sheng; Liao, Xueming; Xie, Xianlong; Mo, Jianlan; Hu, Zhaokun; Dai, Huijun; Pan, Linghui

doi:10.1016/j.intimp.2022.109462

Cited by 3 publications

(1 citation statement)

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“…The degree of lung injury was scored according to alveolar congestion, hemorrhages, neutrophil infiltration and incrassation of the alveolar wall with a five-point score: 0, minimal injury; 1, mild injury; 2, moderate injury; 3, serious injury; and 4, maximal injury. 16 Simultaneously, some lung samples were cut for transmission electron microscope (TEM) scanning to observe ultrastructural changes of lung epithelial cells.…”

Section: Verification Of Animal Modelmentioning

confidence: 99%

Identification of potential biomarkers for nonsurvivor sepsis patients via microarray technology: A study based on GEO datasets

Ma,

Shan,

Luo

et al. 2023

Eur J Inflamm

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Background: The mechanism of sepsis especially non-survivors has not yet been identified. Objective: To identify the key genes concerned with non-survivor sepsis (NSS) and analyze its molecular mechanism. Methods: The original data were obtained from the GEO database to screen deferentially expressed genes (DEGs). GO and KEGG analysis were performed to analyze the functional annotation of DEGs. The protein-protein interaction (PPI) network and related analysis of hub genes were carried out. Further, hub genes were confirmed in the lipopolysaccharide (LPS)-induced septic mice by western blotting and immunohistochemistry. Results: We obtained 188 DEGs and 32 hub genes between NSS patients and healthy volunteers. Among of them, the top 10 hub genes including STAT1, ISG15, HERC1, EIF2AK2, RPL27, LY6E, IFI44L, XAF1, RSAD2 and HERC6 were studied, which predict sepsis based on receiver operator characteristic curve analysis. These hub genes were enriched in positive regulation of biomedical process including translation, response to virus and suppression of mitochondrial depolarization, etc.; cell component including mitochondrial inner membrane; molecular function containing ligase activity, etc. These hub genes are also enriched in influenza A infection and leukocyte trans-endothelial migration. The expression of these hub genes is better involved in a diagnosis of NSS, such as HERC6 (AUC = 0.9753, p = .0007), RPL27 (AUC = 0.9691, p = .0008), ISG15 (AUC = 0.9630, p = .0009), STAT1 (AUC = 0.9383, p = .0017), HERC1 (AUC = 0.9259, p = .0023), and XAF1 (AUC = 0.9259, p = .0023). Furthermore, 20 mg/kg of LPS injection up-regulated the expression of ISG15, RPL27, LY6E and HERC6 in the lung tissues compared with control mice. Conclusion: These identified 188 DEGs and 10 hub genes were associated with NSS, especially ISG15, RPL27, LY6E and HERC6 genes expressed in the lung as the most vulnerable organ.

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Section: Verification Of Animal Modelmentioning

confidence: 99%

Identification of potential biomarkers for nonsurvivor sepsis patients via microarray technology: A study based on GEO datasets

Ma,

Shan,

Luo

et al. 2023

Eur J Inflamm

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Alveolar macrophage-derived gVPLA2 promotes ventilator-induced lung injury via the cPLA2/PGE2 pathway

Han,

Xie,

Shao

et al. 2023

BMC Pulm Med

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Background Ventilator-induced lung injury (VILI) is a clinical complication of mechanical ventilation observed in patients with acute respiratory distress syndrome. It is characterized by inflammation mediated by inflammatory cells and their secreted mediators. Methods To investigate the mechanisms underlying VILI, a C57BL/6J mouse model was induced using high tidal volume (HTV) mechanical ventilation. Mice were pretreated with Clodronate liposomes to deplete alveolar macrophages or administered normal bone marrow-derived macrophages or Group V phospholipase A2 (gVPLA2) intratracheally to inhibit bone marrow-derived macrophages. Lung tissue and bronchoalveolar lavage fluid (BALF) were collected to assess lung injury and measure Ca2 + concentration, gVPLA2, downstream phosphorylated cytoplasmic phospholipase A2 (p-cPLA2), prostaglandin E2 (PGE2), protein expression related to mitochondrial dynamics and mitochondrial damage. Cellular experiments were performed to complement the animal studies. Results Depletion of alveolar macrophages attenuated HTV-induced lung injury and reduced gVPLA2 levels in alveolar lavage fluid. Similarly, inhibition of alveolar macrophage-derived gVPLA2 had a similar effect. Activation of the cPLA2/PGE2/Ca2 + pathway in alveolar epithelial cells by gVPLA2 derived from alveolar macrophages led to disturbances in mitochondrial dynamics and mitochondrial dysfunction. The findings from cellular experiments were consistent with those of animal experiments. Conclusions HTV mechanical ventilation induces the secretion of gVPLA2 by alveolar macrophages, which activates the cPLA2/PGE2/Ca2 + pathway, resulting in mitochondrial dysfunction. These findings provide insights into the pathogenesis of VILI and may contribute to the development of therapeutic strategies for preventing or treating VILI.

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Hippo pathway and NLRP3-driven NETosis in macrophages: Mechanisms of viral pneumonia aggravation

Pan,

Luo,

Wang

et al. 2024

Preprint

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Background Severe viral infections can precipitate acute lung injury, causing substantial morbidity and mortality. NETosis plays a crucial role in defending against pathogens and viruses, but its excessive or dysregulated formation can cause pulmonary damage, with research into its regulation offering potential insights and treatment strategies for viral lung injuries. Methods Elevated levels of NETosis were detected in the peripheral blood of patients with viral pneumonia. To explore the correlation between NETosis and virus-induced acute lung injury, we employed a murine model, administering poly(I:C) (polyinosinic-polycytidylic acid), an artificial substitute for double-stranded RNA, intratracheally to mimic viral pneumonia. Assessment of NETosis biomarkers in afflicted patients and poly(I:C)-stimulated mice was conducted, alongside mechanistic investigations into the involvement of the Hippo signaling pathway, inflammatory factors, and chemokines in the injury process. Cytokine assays, co-culture experiments, and downstream inflammatory mediator analyses were used to ascertain the role of the Hippo pathway in macrophage to mediate NETosis. Results Enhanced expression of NETosis biomarkers was found both in patients with viral pneumonia and in poly(I:C)-stimulated mice. Hippo pathway activation in conjunction with increased levels of inflammatory actors and chemokines was observed in lung tissues of the mouse model. Elevated IL-1β was detected in cells and macrophages isolated from infected mice; this was mitigated by Hippo pathway inhibitors. IL-1β was confirmed to induce NETosis in co-culture experiments, while NLRP3, functioning downstream of the Hippo pathway, mediated its secretion. Patients with viral pneumonia exhibited increased NLRP3 and IL-1β in monocyte-macrophages relative to healthy controls. Conclusions Activated Hippo pathway in macrophages during poly(I:C) exposure upregulates NLRP3 and IL-1β expression to promote the occurrence of NETosis, thereby aggravating virus-induced lung injury. This study identifies a potential target pathway for therapeutic intervention to mitigate lung injury stemming from viral infections.

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Transforming growth factor-β1 attenuates inflammation and lung injury with regulating immune function in ventilator-induced lung injury mice

Cited by 3 publications

References 40 publications

Identification of potential biomarkers for nonsurvivor sepsis patients via microarray technology: A study based on GEO datasets

Identification of potential biomarkers for nonsurvivor sepsis patients via microarray technology: A study based on GEO datasets

Alveolar macrophage-derived gVPLA2 promotes ventilator-induced lung injury via the cPLA2/PGE2 pathway

Hippo pathway and NLRP3-driven NETosis in macrophages: Mechanisms of viral pneumonia aggravation

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